The output MP4s are around 250-500mb, and the quality's fine. The main problem is the buzz or jutter around the outlines of objects, even when the scene is still. Kind of like the second futurama shot on this page:https://trac.handbrake.fr/wiki/Decomb

Having decomb on also seems to have fixed most of the ghosted image between frames but sometimes it seems to have just ignored certain groups of frames, and then it goes back to looking crappy.

I also thought 500mb for 20mins of family guy was a bit big, so I downloaded a torrent (season 1 episode 1), which was about 170mb, and while the resolution was very slightly lower, the quality was perfect - all the outlines of objects were defined and all the motion was smooth.

Would it make a difference if they converted from a region 1 NTSC DVD, or does that not have any effect? If not, what am I doing wrong?

A PAL DVD will probably have NTSC/PAL field blending from the frame rate conversion. It will take more sophisticated handling than Handbrake can deliver (you'll need AviSynth). Use a program like Mpg2Cut2 or DgIndex to extract a 30 second clip from the middle of an episode and post it here.

A PAL DVD will probably have NTSC/PAL field blending from the frame rate conversion. It will take more sophisticated handling than Handbrake can deliver (you'll need AviSynth). Use a program like Mpg2Cut2 or DgIndex to extract a 30 second clip from the middle of an episode and post it here.

Sorry for the late response. The website kept saying "access to ...\newreply.php is prohibited" or something like that.
I've been converting some of the later seasons, and the file size has dropped to between 100-200mb, and the quality's picked up.
So not to sound lazy, but I'm not overly fussed about the quality if it is just the first two seasons, especially with exams coming up

(Just out of interest) Going back to my mention earlier of that torrent I downloaded which seemed very crisp, could I expect to achieve this with AVISynth, or is this most likely because he's converted from NTSC source? Obviously there's the interlaced problem, but there's also this:http://prntscr.com/300ek2
which I described as "buzz", but wasn't sure if that was the right word. Is there any way to get rid of this from the video, or would I need a better source (TV Rip? iTunes?).

Well, it's far from perfect. Look at the windowsill flickering 13 to 16 seconds into the clip. There is still a little ghosting here and there. Those problems probably wouldn't be there if you were starting with the NTSC source.

QTGMC() and SRestore() are two of the hardest AviSynth filters to get set up.